Breast cancer is one of the most common cancers in the United
States, killing an estimated 40,000 women annually, and was newly
diagnosed in approximately 190,000 women in 2009, according to NCI SEER
data (National Cancer Institute Surveillance Epidemiology and End
Results).

To diagnose these cancers, at least 5 times this number will
require a biopsy to determine whether a finding is benign or malignant.
In the U.S. alone, this equates to approximately 1 million breast
biopsies per year.

Non palpable cancers are usually picked up at a screening
mammogram, and there has been a concomitant rise in the number of ductal
carcinoma in situ diagnosed as a side effect of screening, which has
caused some debate. Palpable findings, however, especially in younger
women, occur frequently, and are usually the subject of image-guided
biopsy to make the diagnosis.

As a result, biopsy is commonly used by breast imaging radiologists
and focused on lesions falling into categories 4 (suspicious) and 5
(highly suspicious) of the BIRADS reporting system. (1) Once the
preserve of breast interventionalists, biopsy is now in the
armamentarium of every practicing radiologist interpreting mammograms,
and is a routine part of every practice.

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In performing breast biopsy, the challenges we face on a daily
basis are as follows:

1. Ensuring adequate anesthesia;

2. Preventing bleeding;

3. Obtaining representative sampling of a lesion; and,

4. Ensuring that we achieve radiological-pathological concordance.

We will discuss each of these issues and offer some pointers and
practical advice in this article.

Adequate anesthesia

A patient told that she needs a biopsy suffers considerable
anxiety, as most patients fear that they will be given a cancer
diagnosis. There are even measurable systemic effects from the biopsy
procedure. (2) Therefore, to obtain a good quality biopsy, we need to
ensure that the patient is comfortable during the procedure, being
adequately anesthetized. This applies as much to stereotactic core
biopsy as to magnetic resonance imaging (MRI) guided biopsy, both of
which may take a prolonged time from start to finish.

Local anesthesia (LA) procedures using simple Lidocaine 1%, or
combined with 1:100,000 Epinephrine (EPI) are identical to those of
other radiological procedures. (3-5) As LA is supplied as hydrochloride,
and it must be nonionized to enter the nerve endings, it may be buffered
with 8.4% sodium bicarbonate (Table 1). The resulting reduction in
acidity also assists in reducing the 'burn' associated with
the injection and improved patient comfort.

Another proven method of reducing the discomfort from the LA
injection is to warm the Lidocaine to body temperature before injection.
(6-12)

If using vacuum-assisted biopsy (VAB), due to the dead space of the
needle distal to the sample notch, which may be up to 1 cm, at least 1.5
cm beyond the area being biopsied, should be anesthetized. In practice,
this means using a long needle (eg, spinal needle) and intentionally
injecting beyond the lesion. If you are performing a stereotactic
biopsy, you can inject from the deepest part of the breast adjacent to
the Bucky, all the way out to the skin.

Reduction of residual pain from deep VAB may be mitigated by a
second LA injection. (2) If you are using LA with EPI, avoid intradermal
injection (to lessen the risk of skin necrosis). (13) Sub-dermal
injection does not have the same danger. LA combined with EPI has
several advantages: It reduces bleeding by local vasoconstriction,
prolongs anesthesia to approximately 6 hours, and reduces the systemic
concentration, therefore making it rare for the patient to get toxic
effects.

The syringe of LA can also be used for 'blunt
dissection'--you can lift a mass off an implant/chest wall, or the
skin, by injecting as you advance the needle slowly. Once you obtain a
small, fluid-filled cavity, advance the needle while still injecting.
This technique is similar to the surgical technique of blunt tissue
dissection using forceps rather than a cutting blade.

Practice point: Use a long needle (eg, spinal needle) and
intentionally inject beyond the lesion. If you are performing a
stereotactic biopsy, you can inject from the deepest part of the breast
adjacent to the Bucky, all the way out to the skin.

Difficult areas to anesthetize and the use of regional blocks

Some areas of the breast, in particular the immediate sub-areolar
region, are difficult to anesthetize fully. As a result, if the patient
then has a bad experience with her biopsy, she may never return for
another mammogram.

An alternative technique, known as a regional anesthesia, is a
'Nipple Block.' (14) Your breast surgeon may be willing to
teach this to you.

One of the most effective simple ways of achieving full anesthesia
of the nipple areola complex (NAC) is to use topical Lidocaine, either
as viscous Lidocaine or as a eutectic mixture of local anesthetics
(EMLA, APP Pharmaceuticals) cream. Using EMLA 30 min prior to the
procedure for a sub-areolar mass or a ductogram makes the process easier
for yourself and the patient.

If adequate anesthesia has not been obtained there are two parts of
the nipple block that can assist. The first is to inject in a stepwise
manner, around the nipple areola margin (Figure 1).

The second can achieve complete anesthesia, such that some surgeons
can do a mastectomy. This requires the addition of a pool of 5 ml LA
injected centrally in the breast, in the retroglandular region. This
takes out the penetrating branches of the intercostal nerves. This is
easily achieved under ultrasound guidance from the lateral aspect of the
breast (Figure 2).

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Practice point: Good anesthesia is the key to a cooperative patient
and a successful biopsy, but consider topical LA gels and regional block
if the lesion is sub-areolar in position.

Prevention of bleeding: aspirin, warfarin, and clopidogrel

Any intervention in the breast may be complicated by
hemorrhage/hematoma formation during, or following, the procedure. This
is more common with the use of aspirin, warfarin (Coumadin[TM]) or
clopidogrel (Plavix[TM], Sanofi-Aventis, US).

The first confirmation that breast biopsy was safe to perform in
patients on aspirin, heparin, or warfarin was published in 2000. (15)
This study was from an academic center, but it confirmed something that
had been suspected for a long time.

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The findings were validated in late 2008, when an article from
community practice was published. (16) This article showed that there
was no significant risk of bleeding when patients are on aspirin or
warfarin, and patients only need to be consented for an increased risk
of hemorrhage/hematoma. A patient with a 'therapeutic range'
INR, within 2 weeks of the procedure, is safe to biopsy. The only
patients we still do not like to biopsy without withdrawal of therapy
are those being treated with clopidogrel.

Practice point: Breast biopsy is safe in patients on antiplatelet
or anticoagulant therapy, yet doubts still remain about patients on
clopidogrel.

Representative sampling: Targeting and sampling error

One of the goals of a successful biopsy is to achieve adequate
tissue sampling. This means that enough tissue is excised for
pathological diagnosis. This is referred to as
'representative' sampling.

The choice of modality for biopsy and the size of the needle are
important in obtaining a satisfactory tissue sample.

For ultrasound masses, it is often best to get a margin of a mass
as part of the procedure, especially in the case of stromal sclerosis,
fibrocystic change presenting as a mass, or hamartomas, as the central
part of the mass may look like normal benign tissue under the
microscope, whereas if a margin is included (Figure 3), then the
pathologist may be able to identify a 'mass,' and report it as
such.

Similarly, calcifications are usually sampled by stereotaxis and a
specimen x-ray is obtained to determine whether enough calcification was
sampled to be representative of a lesion. If the calcified area is
visible and biopsied under ultrasound guidance (Figure 4), then a
specimen x-ray should be performed as if it had been performed under
stereotaxis, to document removal of calcifications and representative
sampling.

Needle size makes a difference when it comes to the issue of
underestimation of DCIS or invasive cancer. This is caused by not truly
getting tissue that is a representative sample. Commonly, this occurs in
a patient with suspicious calcifications and a core biopsy of atypical
ductal hyperplasia (ADH), which eventually turns out to be DCIS.

Equally important is the underestimation of invasive disease, when
only DCIS is found at core biopsy. We can reduce this variant of
sampling error by targeting the asymmetric density/mass associated with
suspicious calcifications (where there is an increased chance of finding
invasive cancer at core).17, 18

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Invasive disease is an important diagnosis to make pre-operatively,
as the diagnosis of invasion mandates sentinel lymph node biopsy (SLNB),
which otherwise is not required for 'noninvasive' disease.

Tables 2 and 3 demonstrate the differences between needle size and
estimates of underestimation of ADH and ductal carcinoma in situ (DCIS)
by publication.

Practice point: The larger the needle, the less under-estimation
and, therefore, sampling error. It is important to note that a diagnosis
of ADH currently requires surgical excision. (38) Similar rates are
found in patients having ultrasound or MRI-guided core biopsy. (39-49)

Sampling and unusual histological findings are as follows: The
diagnosis of papilloma, and the role of subsequent surgical excision
remain controversial. There is an even split in papers between excision
and routine follow-up for women with a lesion compatible with a
papilloma on imaging, with a pathology diagnosis of papilloma. (50-61)
However, the diagnosis of atypia or a papillary lesion always requires
surgical excision. (38)

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There are several other reasons for making a surgical excision
following a core biopsy result. This may be to minimize false negative
core biopsy or because of the need to excise surgically despite
nonmalignant diagnosis at core biopsy. Additional reasons are as
follows:

1. Pathologist recommendation,

2. Radiologic pathologic discordance,

3. Histological underestimation, and,

4. Unusual or 'borderline' histological lesions.

Some patients request that a palpable but proven benign lesion be
surgically removed. This is one of the developing indications for the
diagnostic excision of these lesions, either following a benign fine
needle aspiration (FNA) or a core result. (62-65) This is easily
accomplished for lesions under 2 cm, with the reduction in costs
associated with a fast outpatient procedure, and lesser morbidity (there
is less visible scarring; therefore, it is useful in younger adults).
Even if the fibroadenoma cannot be completely removed, the lesion has
been debulked and is usually no longer palpable, and the patient can
feel on the breast that the lump is gone, improving psychological
outcomes.

Recurrence is possible if the lesion is more than 3 cm in size, but
the procedure can be repeated without harm to the patient. (65) The only
exception (by size definition) is the juvenile fibroadenoma, which has a
propensity to local recurrence, even with surgical excision.

Representative biopsy

Especially when performing a biopsy for calcifications, it is
important to consider whether we have obtained a representative
specimen.

Examine the specimen x-ray and compare it with the diagnostic
images. We need to ensure that not only has calcium been harvested, but
also whether the calcium harvested is representative of the lesion.
Calcium then seen on histology can be correlated with that seen on the
mammogram.

Practice point: A practice tip is to compare the specimen x-ray
with the original prebiopsy diagnostic mammogram and determine whether
you have calcium that represents what you see on the spot magnification
films.

Concordance: Rad-path correlation

As the physician responsible for the biopsy, you are required to
determine whether the pathological diagnosis reported to you fits the
radiological findings. Another way of looking at it is to ask the
question: Do the pathology results make sense in light of the clinical
and imaging findings? If yes, there is concordance; if no, there is
discordance. If there is doubt, it is always worth discussing with the
pathologist, and even comparing what is seen under the microscope with
the mammographic findings. One of the best ways to do this is to have a
regular radiological-pathological meeting (Rad-Path) to discuss cases
that are not straightforward. It is a good learning process for both
parties.

Missing calcifications

How do you deal with a case of representative calcification
sampling, seen on specimen x-ray, but a finding of 'no
calcifications seen' on the pathology report?

Ask to x-ray the specimen blocks if there are relatively few
calcifications, or if the initial report is negative. This is best done
in 2 planes--AP and lateral (Figure 5). A relatively high dose is
required, using manual exposure, to get the best possible image quality.
Once calcifications are identified, the blocks can then be returned to
pathology with the specimen block x-rays, with details of which block
contains the calcifications, and at what depth the calcifications are
located in the block.

In Figure 5, the calcification is present but lies very
superficially in one block. The pathologist must be informed that the
calcification lies in the first 1/3 of the block, with one calcification
particle at the anterior edge.

This is an important finding, as when the technician is making the
slides from the blocks, the microtome shavings of the first few slices
are discarded until a contiguous piece of tissue can be cut, and floated
onto the slide. In this way, microcalcifications can be lost. (66) Other
reasons for calcifications going missing are:

Practice point: If you have trouble with missing calcifications in
pathology, x-ray the pathology blocks and check with polarized light for
calcium oxalate.

Conclusion

In performing a breast biopsy, whether it be ultrasound,
stereotactic or MRI-guided core biopsy, radiologists face challenges
with ensuring adequate anesthesia, reduction of bleeding, representative
sampling, and rad/path concordance. Practice points are provided to
assist radiologists in applying the appropriate techniques, upon making
a significant finding in biopsied lesions.

References

(1.) American College of Radiology breast imaging reporting and
data system atlas (BI-RADS Atlas). Reston, VA: American College of
Radiology (ACR); 2003.

Chris I. Flowers, MD, FRCR, is an Associate Professor of
Oncological Science at the University of South Florida, Tampa, and the
Director of Breast Imaging and Research at the Moffitt Cancer Center and
Research Institute, WCB RAD-MD, Tampa, FL.